Round-up Feb 28th – March 6th

The first patient to have undergone a particular gene therapy for sickle cell disease has had his disease reversed, with no symptoms in 15 months. A huge success for a field that has struggled, his treatment involved removing his bone marrow, using a (non-CRISPR) gene therapy technique to remove the genetic variant responsible for the disease, and returning the bone marrow.

686 autism patients sequenced using 10X’s platform for synthetic long read sequencing, one of the largest studies to probe structural variation at scale, revealing a diversity of complex structural variation

The American College of Obsteticians and Gynecologists has recommendedexpanded carrier screening for genetic disorders in all women during and before pregnancy.

Proove, who have $2m a month revenue test to combat opioid addiction based on genetic markers, are under the spotlightfor a series of dodgy practices. Their story is being used as an example of why the FDA is right to think that it needs to regulate the genetic testing space.

February 28th was Rare Disease Day. To mark the occasion Stephen Kingsmore, he of the 26 hour Whole Genome based diagnosis of newborns, complains: “I think the one thing that I would like technology-wise is better software for going from genome sequence to diagnosis. Right now the software systems that we have are not quite good enough to be scaled up to meet the needs of all the children that we could benefit. There is still way too much manual effort involved.”

GenePeeks will let you know how your genome would combine with another — one step beyond carrier screening, the explicit intent is to help you select an egg or sperm donor. They just announced partnershipswith an egg donation agency and a surrogacy.

Data harmonizations remains a key challenge in germline analysis. The $280m Centers for Common Disease Genomics (CCDG) program, who aim to sequence and analyze the data of ~150-200,000 individuals in existing cohorts, have just announcedtheir standard sequence analysis pipeline.

Emory University School of Medicine and genetics/biobanking company Akesogen are partneringon a study of the genetics of diseases that hit later in life, aiming for 100,000 participants.

Noninvasive Prenatal Testing, where the genetics of the fetus is determined based on a sample of the pregnant mother’s blood, has attracted the attentionof the Nuffield Council for Bioethics, who are calling for a moratorium on using it clinically for whole genome sequencing. Currently, the test is only routinely used for detecting trisomies, but whole genome sequencing of the fetus is debatably already here.

Cancer news

It was a big week for fund raising in the noninvasive early cancer detection space, with Freenome raising $65m, and Grail $900m. Grail is using some of the money to repurchase some of Illumina’s stake.

Foundation Medicine reports dataon use of tumor mutation burden for predicting response to checkpoint inhibitor therapy. “In a cohort of 65 metastatic melanoma patients, the median TMB value was 37.9 mut/Mb in the responder group and 6.6 mut/Mb in the non-responder group.” Similar findings for NSCLC and bladder cancer have previously been reported. (The idea is the following: some cancers avoid the immune system via mutations that lead to over-expression of immune checkpoint proteins; in such cancers, drugs that inhibit/block the inhibitory checkpoint molecules work by “taking the breaks off” the immune system; cancerous cells with more mutations produce more immune-reactive neoantigens, i.e. peptides that the immune system recognizes as non-self; the immune system, when let loose, will be better at attacking and destroying these cells.)

Data sharing efforts for cancer genetics: The NCI’s Genomic Data Commonsaims to collect data from >50,000 cases by the end of 2017. Foundation Medicine have contributed data from 18,000 cases; this adds to AACR’s GENIE project, at > 18,000 publicly available samples as of January. Harmonization of data format is one of the key issues. The Global Alliance for Genomic Health sees itself playing the coordinating role across all of these efforts, via the proposed Cancer Gene Trust.

Actionable results are found for large numbers of cancer patients, but only a small fraction go on to have their treatment affected by those tests. GenomeWeb have a nice writeup, summarizing the pitfalls at each stage of the process.

Once upon a time, cancer’s in different parts of the body were studied separately. With the advent of molecular profiling, the role of pathways and particular driver genes lead to a more body-wide approach. A reviewfocusing attention on organ-specific tumorigenesis.

Other Research

The FANTOM project has been investigating long non-coding RNAs, and thinks there may be ~19,000 of them that are functional, and some of which already have evidence of disease association.

What significance GWAS hits? A high-throughput method to detect associations between protein levels and genetic variants (pQTLs). Move over eQTLs.

In Other News

Another milestonein using DNA as a storage medium. Some researchers encoded a bunch of files (including a film) using a method they call DNA fountain, sent the DNA across the country, where it was decoded with zero errors by another group.

By comparing a 45,000 year old wooly mammoth’s genome to a 4,300 year old specimen, researchsuggests that the last Wooly Mammoths (of which the second sample would be one) were so inbred (“low effective population size”) that their genomes were riddled with deleterious mutations, in work that could shed light on conservation efforts for still extant species.

Some local police departments in the US have created their own DNA databases, because getting results of a sample’s match to the state or national data base can take 18 months, and they can turn analysis around in under 1 month by outsourcing to private labs. This is proving controversial, for example with the ACLU filed a lawsuit against San Diego. The concern is that local authorities are side-stepping all the regulations put in place at the state and national levels to protect citizens from a surveillance state.